The felid taxon serves as one of the most important non-primate models available for addressing human infertility issues, especially the phenomenon of teratospermia (a high incidence of ejaculated sperm pleiomorphisms). The domestic cat is also valuable for studying 36 human physiological disorders ranging from hereditary dysfunctions to AIDS. This project focuses on developing a comprehensive understanding of the reproductive biology of the domestic cat and its wild relatives for two purposes. First, a fundamental database on mechanisms related to reproductive challenges, like teratospermia and embryo loss after in vitro fertilization (IVF) provide insight into similar biological events that are quite common in humans. Second, a by-product of such detailed studies is the ability to artificially regulate production and produce cats of biomedical value or rare status (endangered species) by assisted breeding (i.e., artificial insemination, IVF, embryo transfer). Much of the basic information generated in this project has been used for the practical production of (1) cats unable to naturally breed because of genetically-linked dysfunctions (i.e., mucopolysaccharidosis); and (2) endangered species. We also have used these new techniques to consistently produce domestic cat x leopard cat hybrids useful for developing a high resolution genetic linkage map of the domestic cat. The latter will be useful for further understanding the genetic loci involved in neoplastic transformation and other disease states. During the past year, studies focused on (1) understanding the pharmacokinetics and physiological effects of exogenous gonadotropins, including on ovarian function and embryo quality; and (2) identifying the physiological characteristics of the maternal environment that are most compatible with embryo survival after IVF/embryo transfer. The site of sperm dysfunction in structurally normal spermatozoa of teratospermic males also was determined. These sperm were compromised in tyrosine kinase signaling that adversely affected their ability to undergo the acrosome reaction and, thus, fertilization. Studies are in progress to circumvent the oocyte's protective zona pellucida using intracytoplasmic sperm injection, thereby determining the ability of artificially-delivered sperm from teratospermic ejaculates to fertilize and produce developmentally-normal embryos. Results will have application to enhancing reproduction in males experiencing teratospermia, a common condition in humans, laboratory cats used as animal models, and endangered felids.